Molar hypomineralisation (MH) is becoming globally recognised as a significant public health problem linked to childhood tooth decay. However, with causation and pathogenesis unclear after 100 years ...of investigation, better pathological understanding is needed if MH is to become preventable. Our studies have implicated serum albumin in an extracellular pathomechanism for chalky enamel, opposing longheld dogma about systemic injury to enamel-forming cells. Hypothesising that chalky enamel arises through developmental exposure to serum albumin, this study used biochemical approaches to characterise demarcated opacities from 6-year molars. Addressing contradictory literature, normal enamel was found to completely lack albumin subject to removal of surface contamination. Querying surface permeability, intact opacities were found to lack salivary amylase, indicating that “enamel albumin” had become entrapped before tooth eruption. Thirdly, comparative profiling of chalky and hard-white enamel supported a dose-response relationship between albumin and clinical hardness of opacities. Moreover, albumin abundance delineated chalky enamel from white transitional enamel at opacity borders. Finally, addressing the corollary that enamel albumin had been entrapped for several years, clear signs of molecular ageing (oxidative aggregation and fragmentation) were identified. By establishing aged albumin as a biomarker for chalky enamel, these findings hold methodological, clinical, and aetiological significance. Foremost, direct inhibition of enamel-crystal growth by albumin (here termed “mineralisation poisoning”) at last provides a cogent explanation for the clinical presentation of demarcated opacities. Together, these findings justify pursuit of an extracellular paradigm for the pathogenesis of MH and offer exciting new prospects for alleviating childhood tooth decay through medical prevention of MH.
Molar Hypomineralisation (MH) is gaining cross-sector attention as a global health problem, making deeper enquiry into its prevention a research priority. However, causation and pathogenesis of MH ...remain unclear despite 100 years of investigation into “chalky” dental enamel. Contradicting aetiological dogma involving disrupted enamel-forming cells (ameloblasts), our earlier biochemical analysis of chalky enamel opacities implicated extracellular serum albumin in enamel hypomineralisation. This study sought evidence that the albumin found in chalky enamel reflected causal events during enamel development rather than later association with pre-existing enamel porosity. Hypothesising that blood-derived albumin infiltrates immature enamel and directly blocks its hardening, we developed a “molecular timestamping” method that quantifies the adult and fetal isoforms of serum albumin ratiometrically. Applying this novel approach to 6-year molars, both isoforms of albumin were detectable in 6 of 8 chalky opacities examined (corresponding to 4 of 5 cases), indicating developmental acquisition during early infancy. Addressing protein survival,
in vitro
analysis showed that, like adult albumin, the fetal isoform (alpha-fetoprotein) bound hydroxyapatite avidly and was resistant to kallikrein-4, the pivotal protease involved in enamel hardening. These results shift primary attention from ameloblast injury and indicate instead that an extracellular mechanism involving localised exposure of immature enamel to serum albumin constitutes the crux of MH pathogenesis. Together, our pathomechanistic findings plus the biomarker approach for onset timing open a new direction for aetiological investigations into the medical prevention of MH.
Purpose of the Review
Compare pathophysiology for infectious and noninfectious demineralization disease relative to mineral maintenance, physiologic fluoride levels, and mechanical degradation.
...Recent Findings
Environmental acidity, biomechanics, and intercrystalline percolation of endemic fluoride regulate resistance to demineralization relative to osteopenia, noncarious cervical lesions, and dental caries.
Summary
Demineralization is the most prevalent chronic disease in the world: osteoporosis (OP) >10%, dental caries ~100%. OP is severely debilitating while caries is potentially fatal. Mineralized tissues have a common physiology: cell-mediated apposition, protein matrix, fluid logistics (blood, saliva), intercrystalline ion percolation, cyclic demineralization/remineralization, and acid-based degradation (microbes, clastic cells). Etiology of demineralization involves fluid percolation, metabolism, homeostasis, biomechanics, mechanical wear (attrition or abrasion), and biofilm-related infections. Bone mineral density measurement assesses skeletal mass. Attrition, abrasion, erosion, and abfraction are diagnosed visually, but invisible subsurface caries <400μm cannot be detected. Controlling demineralization at all levels is an important horizon for cost-effective wellness worldwide.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Purpose of Review
Compare noninfectious (part I) to infectious (part II) demineralization of bones and teeth. Evaluate similarities and differences in the expression of hard tissue degradation for ...the two most common chronic demineralization diseases: osteoporosis and dental caries.
Recent Findings
The physiology of demineralization is similar for the sterile skeleton compared to the septic dentition. Superimposing the pathologic variable of infection reveals a unique pathophysiology for dental caries.
Summary
Mineralized tissues are compromised by microdamage, demineralization, and infection. Osseous tissues remodel (turnover) to maintain structural integrity, but the heavily loaded dentition does not turnover so it is ultimately at risk of collapse. A carious tooth is a potential vector for periapical infection that may be life-threatening. Insipient caries is initiated as a subsurface decalcification in enamel that is not detectable until a depth of ~400μm when it becomes visible as a white spot. Reliable detection and remineralization of invisible caries would advance cost-effective wellness worldwide.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•CSF D-dimer levels are elevated in patients that develop DCI.•CSF plasminogen is not predictive of DCI.•CSF D-dimer/plasminogen ratio is predictive of DCI.
Delayed cerebral ischaemia (DCI) after ...aneurysmal subarachnoid haemorrhage (aSAH) is a major contributor to morbidity and mortality. It is currently not possible to reliably predict patients at risk of DCI after aSAH. The aim of this study was to quantify cerebrospinal fluid (CSF) D-Dimer and plasminogen levels and to investigate any association with development of DCI. Cerebrospinal fluid (CSF) samples collected from 30 patients within 72 h post-aSAH (n = 13 DCI and n = 17 non-DCI patients) were analysed. DCI was diagnosed when angiographic vasospasm was detected in the presence of new onset neurological deficit. Enzyme-linked immunosorbent assays were used to quantify D-dimer concentrations while western blotting was used to quantify plasminogen levels. Significant differences in CSF proteins between DCI and non-DCI cohorts were verified using Mann-Whitney test. Sensitivity and specificity of these proteins for detecting DCI was examined using a ROC curve and verified with a Fischer’s exact test. CSF levels of D-dimer within 72 h post aSAH were significantly elevated in DCI patients (54.29 ng/ml, 25.35–105.88 ng/ml) compared to non-DCI patients (26.75 ng/ml, 6.9–45.08 ng/ml) p = 0.03. In our sample population, D-dimer levels above 41.1 ng/ml had a sensitivity of 69.2% and specificity of 75% for predicting DCI. CSF levels of plasminogen (DCI: 0.50 signal-intensity/μl, 0.20–0.73 signal-intensity/μl, non-DCI: 0.28 signal-intensity/μl, 0.22–0.54 signal-intensity/μl) did not differ between the DCI and non-DCI cohort (p > 0.05). Our study suggests that elevated D-dimer in the first 72 h after aSAH may be a potential predictive biomarker for DCI.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Developmental dental defects (DDDs, hereafter "D3s") hold significance for scientists and practitioners from both medicine and dentistry. Although, attention has classically dwelt on three other D3s ...(amelogenesis imperfecta, dental fluorosis, and enamel hypoplasia), dental interest has recently swung toward Molar Hypomineralisation (MH), a prevalent condition characterised by well-delineated ("demarcated") opacities in enamel. MH imposes a significant burden on global health and has potential to become medically preventable, being linked to infantile illness. Yet even in medico-dental research communities there is only narrow awareness of this childhood problem and its link to tooth decay, and of allied research opportunities. Major knowledge gaps exist at population, case and tooth levels and salient information from enamel researchers has sometimes been omitted from clinically-oriented conclusions. From our perspective, a cross-sector translational approach is required to address these complex inadequacies effectively, with the ultimate aim of prevention. Drawing on experience with a translational research network spanning Australia and New Zealand (The D3 Group;
), we firstly depict MH as a silent public health problem that is generally more concerning than the three classical D3s. Second, we argue that diverse research inputs are needed to undertake a multi-faceted attack on this problem, and outline demarcated opacities as the central research target. Third, we suggest that, given past victories studying other dental conditions, enamel researchers stand to make crucial contributions to the understanding and prevention of MH. Finally, to focus geographically diverse research interests onto this nascent field, further internationalisation of The D3 Group is warranted.
The purpose of this study was to quantify and qualify the 3-dimensional (3D) condylar changes using mandibular 3D regional superimposition techniques in adolescent patients with Class II Division 1 ...malocclusions treated with either a 2-phase or single-phase approach.
Twenty patients with Herbst appliances who met the inclusion criteria and had cone-beam computed tomography (CBCT) images taken before, 8 weeks after Herbst removal, and after the completion of multibracket appliance treatment constituted the Herbst group. They were compared with 11 subjects with Class II malocclusion who were treated with elastics and multibracket appliances and who had CBCT images taken before and after treatment. Three-dimensional models generated from the CBCT images were registered on the mandible using 3D voxel-based superimposition techniques and analyzed using semitransparent overlays and point-to-point measurements.
The magnitude of lateral condylar growth during the orthodontic phase (T2-T3) was greater than that during the orthopedic phase (T1-T2) for all condylar fiducials with the exception of the superior condyle (P <0.05). Conversely, posterior condylar growth was greater during the orthopedic phase than the subsequent orthodontic phase for all condylar fiducials (P <0.05). The magnitude of vertical condylar development was similar during both the orthopedic (T1-T2) and orthodontic phases (T2-T3) across all condylar fiducials (P <0.05). Posterior condylar growth during the orthodontic phase (T2-T3) of the 2-phase approach decreased for all condylar fiducials with the exception of the posterior condylar fiducial (P <0.05) when compared with the single-phase approach.
Two-phase treatment using a Herbst appliance accelerates condylar growth when compared with a single-phase regime with Class II elastics. Whereas the posterior condylar growth manifested primarily during the orthopedic phase, the vertical condylar gains occurred in equal magnitude throughout both phases of the 2-phase treatment regime.
•This is a follow-up study of Atresh et al, previously published in AJO-DO in August 2018.•Adolescent subjects with Class II malocclusions were treated with the Herbst appliance or Class II elastics with 3D mandibular voxel-based superimposition used to describe condylar changes.•Two-phase treatment using a Herbst appliance accelerated condylar growth when compared to single-phase treatment with Class II elastics.•Posterior condylar growth manifested primarily during the orthopedic phase of the 2-phase regime.•Vertical condylar gains occurred equally in both orthopedic and orthodontic phases of the 2-phase treatment regime.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Background and objectives: Many orthodontic bracket-bonding materials are available for clinical use. The current study aimed to assess the preferences and factors contributing to the ...clinical choice of bracket bonding material. Methods: Eight bracket bonding materials were trialled by 15 participants. The handling properties and overall ease of use of each material were scored by the participants on a Visual Analogue Scale (VAS). The participants also responded to a questionnaire regarding the use and perceptions of resin-modified glass ionomer cements (RMGICs) for bracket bonding. A quantitative analysis was conducted on the responses to the questionnaire. Results: Of all materials trialled, there was a consistent preference for the handling of resin composite (RC) materials. Fuji ® II LC was the highest rated RMGIC material and was considered similar to RC materials for ease of handling. Conclusions: Fuji ® II LC may be a suitable alternative to RC materials for orthodontic bracket bonding. Further research is required to assess and produce bonding materials possessing anti-cariogenic properties along with comparable handling properties to bracket bonding materials that are currently preferred.
The protease kallikrein 4 (KLK4) plays a pivotal role during dental enamel formation by degrading the major enamel protein, amelogenin, prior to the final steps of enamel hardening. KLK4 dysfunction ...is known to cause some types of developmental defect in enamel but the mechanisms responsible for transient retention of KLK4 in semi-hardened enamel matrix remain unclear. To address contradictory reports about the affinity of KLK4 for enamel hydroxyapatite-like mineral, we used pure components in quasi-physiological conditions and found that KLK4 binds hydroxyapatite directly. Hypothesising KLK4 self-destructs once amelogenin is degraded, biochemical analyses revealed that KLK4 progressively lost activity, became aggregated, and autofragmented when incubated without substrate in both the presence and absence of reducer. However, with non-ionic detergent present as proxy substrate, KLK4 remained active and intact throughout. These findings prompt a new mechanistic model and line of enquiry into the role of KLK4 in enamel hardening and malformation.
•Contradictions about KLK4 binding to hydroxyapatite were resolved biochemically.•A proxy substrate stabilises KLK4 against inactivation, aggregation and autolysis.•A mechanistic model involving KLK4 retention and autodegradation is proposed.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK, ZRSKP
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